Pathophysiological mechanisms of ultra-early transient hyperperfusion after cerebral ischemia-reperfusion in rats

Objective To investigate the pathophysiological mechanisms of spontaneous transient hyperperfusion after cerebral ischemia-reperfusion in rats. Methods Fifty-two SD rats were randomly allocated into sham-operation （group A）, cerebral ischemia 2-hour （group B）, and cerebral ischemia 6-hour （group C） groups. Group B were redivided into 0-, 0.5-, 1 -, 2-, 4-, 6-, and 24-hour subgroups according to the reperfusion time; group C were redivided into 0-, 0.5-, 1 -, 2-, and 24-hour subgroups according to the reperfusion time （n = 4 in each subgroup）. Multislice spiral CT perfusion imaging （CTPI） was performed at different time points after ischemia-reperfusion in each group. After completing the scanning, the rats were sacrificed immediately for optical and electron microscopy examinations. Results In group A, compared to the contralateral sides, there were no significant differences in the relative value of the cerebral blood flow parameters and the results of optical and electron microscopy in the shamoperated regions. In group B, the relative cerebral blood flow （rCBF） and relative cerebral blood volume （rCBV） in the ischemic core area were increased gradually with the extension of reperfusion time. The relative mean transit time （rMTF） and the relative time to peak （rTIP） were decreased gradually. There were no significant differences compared to group A at 6-hour after reperfusion, The optical and electron microscopy revealed that neuronal density in the ischemic core area in group B were decreased, part of the cell volume enlarged and showed vacuolated changes, and part of the neuronal cell bodies and nuclei shrinked, rCBF in the ischemic core area still maintained lower level with the extension of reperfusion time in group C. The ischemic core area showed the increased transient rCBV and rCBV at 0.5 hour after reperfusion in group B and C. The optical and electron microscopy showed that the ischemic core area presented a large number of necrotic and apoptotic cells, and inflammatory cell infiltration. At 6 hours after reperfusion in group B, the increased blood density was observed under the electron microscope in the ischemic core area, showing capillary engorgement and increased pressure. Conclusions The dynamic changes of CTPI in the process of rat middle cerebral artery occlusion and reperfusion have a certain correlation with the pathological mechanisms of injury. The ultra-early spontaneous and transient hyperperfusion after cerebral ischemia-reperfusion in rats is associated with the transient inflammatory hyperemia after repeffusion injury. Key words: Brain ischemia;  Reperfusion injury;  Tomography, X-ray computed;  Rats